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HRP20200934T1 - Solid forms and formulations of (s)-4-(8-amino-3-(1 -(but-2-ynoyl)pyrrolidin-2-yl)imidazo[1,5-a]pyrazin-1-yl)-n-(pyridin-2-yl)benzamide - Google Patents

Solid forms and formulations of (s)-4-(8-amino-3-(1 -(but-2-ynoyl)pyrrolidin-2-yl)imidazo[1,5-a]pyrazin-1-yl)-n-(pyridin-2-yl)benzamide Download PDF

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HRP20200934T1
HRP20200934T1 HRP20200934TT HRP20200934T HRP20200934T1 HR P20200934 T1 HRP20200934 T1 HR P20200934T1 HR P20200934T T HRP20200934T T HR P20200934TT HR P20200934 T HRP20200934 T HR P20200934T HR P20200934 T1 HRP20200934 T1 HR P20200934T1
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Croatia
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cancer
preparation according
pyrazin
imidazo
pyrrolidin
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HRP20200934TT
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Croatian (hr)
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Tim INGALLINERA
Tjeerd A. Barf
Edwin Aret
Cecile Krejsa
Jerry Evarts
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Acerta Pharma B.V.
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Publication of HRP20200934T1 publication Critical patent/HRP20200934T1/en

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Claims (17)

1. Pripravak koji sadrži slobodnu bazu kristalnog (S)-4-(8-amino-3-(1-(but-2-inoil)pirolidin-2-il)imidazo[1,5-a]pirazin-1-il)-N-(piridin-2-il)benzamida pri čemu je slobodna baza kristalnog (S)-4-(8-amino-3-(1-(but-2-inoil)pirolidin-2-il)imidazo[1,5-a]pirazin-1-il)-N-(piridin-2-il)benzamida naznačena time što ima prijenos uzorka rendgenske difrakcije praha koji sadrži vrhove kod 6.4, 8.6, 10.5, 11.6, i 15.7 °2θ ± 0.2 °2θ, pri čemu je uzorak rendgenske difrakcije praha dobiven korištenjem izvora Cu-Kα1 zračenja.1. A preparation containing the free base of crystalline (S)-4-(8-amino-3-(1-(but-2-inoyl)pyrrolidin-2-yl)imidazo[1,5-a]pyrazin-1-yl )-N-(pyridin-2-yl)benzamide, wherein the free base of crystalline (S)-4-(8-amino-3-(1-(but-2-inoyl)pyrrolidin-2-yl)imidazo[1 ,5-a]pyrazin-1-yl)-N-(pyridin-2-yl)benzamide indicated by having a transmission X-ray powder diffraction pattern containing peaks at 6.4, 8.6, 10.5, 11.6, and 15.7 °2θ ± 0.2 ° 2θ, where the X-ray powder diffraction pattern was obtained using a Cu-Kα1 radiation source. 2. Pripravak prema patentnom zahtjevu 1, pri čemu je slobodna baza kristalnog (S)-4-(8-amino-3-(1-(but-2-inoil)pirolidin-2-il)imidazo[1,5-a]pirazin-1-il)-N-(piridin-2-il)benzamida naznačena time što ima prijenos uzorka rendgenske difrakcije praha koji dalje sadrži vrhove kod 10.9, 12.7, 13.4, 14.3, 14.9, i 18.2 °2θ ± 0.2 °2θ, pri čemu je uzorak rendgenske difrakcije praha dobiven korištenjem izvora Cu-Kα1 zračenja.2. The preparation according to claim 1, wherein the free base is crystalline (S)-4-(8-amino-3-(1-(but-2-inoyl)pyrrolidin-2-yl)imidazo[1,5-a ]pyrazin-1-yl)-N-(pyridin-2-yl)benzamide indicated by having a transmission X-ray powder diffraction pattern that further contains peaks at 10.9, 12.7, 13.4, 14.3, 14.9, and 18.2 °2θ ± 0.2 °2θ , where the X-ray powder diffraction pattern was obtained using a Cu-Kα1 radiation source. 3. Pripravak prema bilo kojem od patentnih zahtjeva 1 ili 2, pri čemu je slobodna baza kristalnog (S)-4-(8-amino-3-(1-(but-2-inoil)pirolidin-2-il)imidazo[1,5-a]pirazin-1-il)-N-(piridin-2-il)benzamida naznačena time što ima prijenos uzorka rendgenske difrakcije praha koji dalje sadrži jedan ili više vrhova odabranih iz skupine koja se sastoji od 11.3, 15.1, 16.1, 17.3, 19.2, 19.4, 19.8, 20.7, 21.1, 21.4, 21.6, 21.9, 22.6, 23.3, 23.6, 24.9, 25.2, 25.4, 25.7, 26.1, 26.4, 26.8, 26.9, 27.7, 28.6, 29.1, 29.4, 30.1, 30.5, 31.7, 31.9, 32.2, 32.6, 33.1, 33.4, 34.5, 35.9, 36.1, 36.8, 37.4, 38.1, 38.9, i 39.5 °2θ ± 0.2 °2θ, pri čemu je uzorak rendgenske difrakcije praha dobiven korištenjem izvora Cu-Kα1 zračenja.3. The preparation according to any one of claims 1 or 2, wherein the free base is crystalline (S)-4-(8-amino-3-(1-(but-2-inoyl)pyrrolidin-2-yl)imidazo[ 1,5-a]pyrazin-1-yl)-N-(pyridin-2-yl)benzamide characterized by having a transmission X-ray powder diffraction pattern further comprising one or more peaks selected from the group consisting of 11.3, 15.1, 16.1, 17.3, 19.2, 19.4, 19.8, 20.7, 21.1, 21.4, 21.6, 21.9, 22.6, 23.3, 23.6, 24.9, 25.2, 25.4, 25.7, 26.1, 26.4, 26.8, 26.9, 27.7, 28.6, 29.1, 29.4, 29.4, 29.4 30.1, 30.5, 31.7, 31.9, 32.2, 32.6, 33.1, 33.4, 34.5, 35.9, 36.1, 36.8, 37.4, 38.1, 38.9, and 39.5 °2θ ± 0.2 °2θ, where the X-ray powder diffraction pattern was obtained using a Cu source. -Kα1 radiation. 4. Pripravak prema bilo kojem od patentnih zahtjeva 1 do 3, pri čemu je slobodna baza kristalnog (S)-4-(8-amino-3-(1-(but-2-inoil)pirolidin-2-il)imidazo[1,5-a]pirazin-1-il)-N-(piridin-2-il)benzamida naznačena time što ima Ramanov spektar koji sadrži vrhove kod 1620, 1609, 1547, 1514, i 1495 cm-1 ± 2 cm-1.4. The preparation according to any one of claims 1 to 3, wherein the free base is crystalline (S)-4-(8-amino-3-(1-(but-2-inoyl)pyrrolidin-2-yl)imidazo[ 1,5-a]pyrazin-1-yl)-N-(pyridin-2-yl)benzamide characterized by having a Raman spectrum containing peaks at 1620, 1609, 1547, 1514, and 1495 cm-1 ± 2 cm- 1. 5. Pripravak prema patentnom zahtjevu 4, pri čemu je slobodna baza kristalnog (S)-4-(8-amino-3-(1-(but-2-inoil)pirolidin-2-il)imidazo[1,5-a]pirazin-1-il)-N-(piridin-2-il)benzamida naznačena time što ima Ramanov spektar koji dalje sadrži jedan ili više vrhova odabranih iz skupine koja se sastoji od 1680, 1574, 1454, 1433, 1351, 1312, 1255, 1232, 1187, 1046, 995, 706, 406, i 280 cm-1 ± 2 cm-1.5. The preparation according to patent claim 4, wherein the free base of crystalline (S)-4-(8-amino-3-(1-(but-2-inoyl)pyrrolidin-2-yl)imidazo[1,5-a ]pyrazin-1-yl)-N-(pyridin-2-yl)benzamide characterized by having a Raman spectrum further comprising one or more peaks selected from the group consisting of 1680, 1574, 1454, 1433, 1351, 1312, 1255, 1232, 1187, 1046, 995, 706, 406, and 280 cm-1 ± 2 cm-1. 6. Pripravak prema bilo kojem od patentnih zahtjeva 1 do 5, pri čemu je slobodna baza kristalnog (S)-4-(8-amino-3-(1-(but-2-inoil)pirolidin-2-il)imidazo[1,5-a]pirazin-1-il)-N-(piridin-2-il)benzamida naznačena time što ima infracrveni (IR) spektar koji sadrži vrhove kod 1621, 1608, 1403, 1303, i 764 cm-1 ± 4 cm-1.6. The preparation according to any one of claims 1 to 5, wherein the free base is crystalline (S)-4-(8-amino-3-(1-(but-2-inoyl)pyrrolidin-2-yl)imidazo[ 1,5-a]pyrazin-1-yl)-N-(pyridin-2-yl)benzamide characterized by having an infrared (IR) spectrum containing peaks at 1621, 1608, 1403, 1303, and 764 cm-1 ± 4 cm-1. 7. Pripravak prema patentnom zahtjevu 6, pri čemu je slobodna baza kristalnog (S)-4-(8-amino-3-(1-(but-2-inoil)pirolidin-2-il)imidazo[1,5-a]pirazin-1-il)-N-(piridin-2-il)benzamida naznačena time što ima IR spektar koji dalje uključuje jedan ili više vrhova odabranih iz skupine koja se sastoji od 3367, 3089, 2246, 1682, 1574, 1514, 1504, 1454, 1428, 1345, 1248, 1194, 1177, 1149, 1109, 1049, 1023, 1003, 947, 900, 858, 842, 816, 734, 729, 701, 689, 665, 623, i 612 cm-1 ± 4 cm-1.7. The preparation according to claim 6, wherein the free base is crystalline (S)-4-(8-amino-3-(1-(but-2-inoyl)pyrrolidin-2-yl)imidazo[1,5-a ]pyrazin-1-yl)-N-(pyridin-2-yl)benzamide characterized by having an IR spectrum further comprising one or more peaks selected from the group consisting of 3367, 3089, 2246, 1682, 1574, 1514, 1504, 1454, 1428, 1345, 1248, 1194, 1177, 1149, 1109, 1049, 1023, 1003, 947, 900, 858, 842, 816, 734, 729, 701, 689, 665, and 623 cm. 1 ± 4 cm-1. 8. Pripravak prema bilo kojem od patentnih zahtjeva 1 do 7, pri čemu je slobodna baza kristalnog (S)-4-(8-amino-3-(1-(but-2-inoil)pirolidin-2-il)imidazo[1,5-a]pirazin-1-il)-N-(piridin-2-il)benzamida, te je dodatno naznačen nepostojanjem vode u kristalnoj strukturi.8. A preparation according to any one of claims 1 to 7, wherein the free base is crystalline (S)-4-(8-amino-3-(1-(but-2-inoyl)pyrrolidin-2-yl)imidazo[ 1,5-a]pyrazin-1-yl)-N-(pyridin-2-yl)benzamide, and is additionally indicated by the absence of water in the crystal structure. 9. Pripravak prema bilo kojem od patentnih zahtjeva 1 do 8, naznačen time što nadalje sadrži ekstra granularni acidulant.9. The preparation according to any one of claims 1 to 8, characterized in that it further contains an extra granular acidulant. 10. Pripravak prema patentnom zahtjevu 9, naznačen time što je ekstra granularni acidulant izabran iz skupine koja se sastoji od fumarne kiseline, jantarne kiseline, -vinske kiseline, L-vinske kiseline, racemske vinske kiseline, askorbinske kiseline, izaskorbinske kiseline (poznate i kao eritorbinska kiselina i D-araboaskorbinska kiselina), alginske kiseline ili njihove soli, Protacid F 120 NM, Protacid AR 1112 (također poznat kao Kelacid NF), i Carbopol 971P (karboksipolimetilen), i njihovih kombinacija.10. The preparation according to claim 9, characterized in that the extra granular acidulant is selected from the group consisting of fumaric acid, succinic acid, -tartaric acid, L-tartaric acid, racemic tartaric acid, ascorbic acid, isascorbic acid (also known as erythorbic acid and D-araboascorbic acid), alginic acids or their salts, Protacid F 120 NM, Protacid AR 1112 (also known as Kelacid NF), and Carbopol 971P (carboxypolymethylene), and combinations thereof. 11. Pripravak prema patentnom zahtjevu 9, naznačen time što je ekstra granularni acidulant alginska kiselina, ili njezina natrijeva ili kalijeva sol, u koncentraciji između 5% do 33% težinski.11. The preparation according to claim 9, characterized in that the extra granular acidulant is alginic acid, or its sodium or potassium salt, in a concentration between 5% to 33% by weight. 12. Pripravak prema bilo kojem od patentnih zahtjeva 1 do 11, naznačen time što pripravak nadalje sadrži najmanje jednu farmaceutski prihvatljivu pomoćnu tvar.12. The preparation according to any one of patent claims 1 to 11, characterized in that the preparation further contains at least one pharmaceutically acceptable excipient. 13. Pripravak prema patentnom zahtjevu 12 naznačen time što se upotrebljava u liječenju hiperproliferativne bolesti, pri čemu je hiperproliferativna bolest odabrana iz skupine koja sadrži kroničnu limfocitnu leukemiju, ne-Hodgkinov limfom, difuzni veliki B-stanični limfom, limfom plaštenih stanica, folikularni limfom, B limfoproliferativnu bolest B-stanica, akutnu limfoblastičnu leukemiju B-stanica, Waldenstromovu makroglobulinemiju, Burkittovu leukemiju, Hodgkinovu bolest, multipli mijelom, akutnu mijeloičnu leukemiju, juvenilnu mijelomonocitnu leukemiju, leukemiju vlasastih stanica, mastocitnu leukemiju, mastocitozu, mijeloproliferativne poremećaje (MPD), mijeloproliferativne neoplazme, policitemija vera (PV), esencijalnu trombocitemiju (ET), primarnu mijelofibrozu (PMF), mijelodisplastični sindrom, kroničnu mijeloičnu leukemiju (BCR-ABL1-pozitivna), kroničnu neutrofilnu leukemiju, kroničnu eozinofilnu leukemiju, limfom primarnog središnjeg živčanog sustava (CNS), primarni multifokalni limfom perifernog živčanog sustava (PNS), rak timusa, rak mozga, glioblastom, rak pluća, karcinom skvamoznih stanica, rak kože (npr., melanom), rak očiju, retinoblastom, intraokularni melanom, karcinom usne šupljine i orofarinksa, rak mokraćnog mjehura, rak želuca, karcinom gušterače, karcinom dojke, rak grlića maternice, rak glave i vrata, renalni karcinom, rak bubrega, rak jetre, rak jajnika, rak prostate, rak debelog crijeva, rak kostiju (npr., metastatski rak kostiju), rak jednjaka, rak testisa, ginekološki karcinom, rak štitnjače, rak epidermoida, karcinom povezan s AIDS-om (npr., limfom), virusom izazvan karcinom grlića maternice (humani papiloma virus), nazofaringealni karcinom (virus Epstein-Barr), Kaposijev sarkom, primarni izljevni limfom (Kaposijev sarkom herpes virus), hepatocelularni karcinom (virusi hepatitisa B i hepatitisa C), leukemije T-stanica (virus ljudske leukemije stanica T tipa 1), benignu hiperplaziju kože, restenozu, benignu hipertrofiju prostate, angiogenezu tumora, kroničnu upalnu bolest, reumatoidni artritis, aterosklerozu, upalnu bolest crijeva, kožne bolesti poput psorijaze, ekcema i sklerodermije, dijabetes, dijabetičku retinopatiju, retinopatiju nedonoščadi, staračku makularnu degeneraciju, hemangiom, ulcerozni kolitis, atopijski dermatitis, pouchitis, spondiloartritis, uveitis, Behcetovu bolest, reumatsku polimialgiju, arteritis orijaških stanica, sarkoidozu, Kawasakijevu bolest, juvenilni idiopatski artritis, hidratenitis suppurativa, Sjögrenov sindrom, psorijatični artritis, juvenilni reumatoidni artritis, ankilozirajući spondilitis, Crohnovu bolest, lupus i lupusni nefritis.13. The preparation according to patent claim 12 characterized in that it is used in the treatment of a hyperproliferative disease, wherein the hyperproliferative disease is selected from the group containing chronic lymphocytic leukemia, non-Hodgkin's lymphoma, diffuse large B-cell lymphoma, mantle cell lymphoma, follicular lymphoma, B-cell B-cell lymphoproliferative disease, B-cell acute lymphoblastic leukemia, Waldenstrom's macroglobulinemia, Burkitt's leukemia, Hodgkin's disease, multiple myeloma, acute myeloid leukemia, juvenile myelomonocytic leukemia, hairy cell leukemia, mast cell leukemia, mastocytosis, myeloproliferative disorders (MPD), myeloproliferative neoplasms, polycythemia vera (PV), essential thrombocythemia (ET), primary myelofibrosis (PMF), myelodysplastic syndrome, chronic myeloid leukemia (BCR-ABL1-positive), chronic neutrophilic leukemia, chronic eosinophilic leukemia, primary central nervous system (CNS) lymphoma , primary multifocal nor peripheral nervous system (PNS) lymphoma, thymus cancer, brain cancer, glioblastoma, lung cancer, squamous cell carcinoma, skin cancer (eg, melanoma), eye cancer, retinoblastoma, intraocular melanoma, oral cavity and oropharyngeal carcinoma, bladder cancer , stomach cancer, pancreatic cancer, breast cancer, cervical cancer, head and neck cancer, renal cancer, kidney cancer, liver cancer, ovarian cancer, prostate cancer, colon cancer, bone cancer (eg, metastatic bone cancer), cancer esophagus, testicular cancer, gynecological cancer, thyroid cancer, epidermoid cancer, AIDS-related cancer (eg, lymphoma), virus-induced cervical cancer (human papilloma virus), nasopharyngeal cancer (Epstein-Barr virus), Kaposi's sarcoma, primary effusion lymphoma (Kaposi's sarcoma herpes virus), hepatocellular carcinoma (hepatitis B and hepatitis C viruses), T-cell leukemias (human T-cell leukemia virus type 1), benign skin hyperplasia, restenosis, benign prostatic hypertrophy, angiogenic tumors, chronic inflammatory disease, rheumatoid arthritis, atherosclerosis, inflammatory bowel disease, skin diseases such as psoriasis, eczema and scleroderma, diabetes, diabetic retinopathy, retinopathy of prematurity, age-related macular degeneration, hemangioma, ulcerative colitis, atopic dermatitis, pouchitis, spondyloarthritis, uveitis , Behçet's disease, polymyalgia rheumatica, giant cell arteritis, sarcoidosis, Kawasaki disease, juvenile idiopathic arthritis, hydratenitis suppurativa, Sjögren's syndrome, psoriatic arthritis, juvenile rheumatoid arthritis, ankylosing spondylitis, Crohn's disease, lupus and lupus nephritis. 14. Pripravak prema patentnom zahtjevu 12 naznačen time što se upotrebljava u liječenju hiperproliferativne bolesti, pri čemu je hiperproliferativna bolest kronična limfocitna leukemija.14. The preparation according to patent claim 12, characterized in that it is used in the treatment of a hyperproliferative disease, wherein the hyperproliferative disease is chronic lymphocytic leukemia. 15. Pripravak prema patentnom zahtjevu 12 naznačen time što se upotrebljava u liječenju hiperproliferativne bolesti, pri čemu je hiperproliferativna bolest limfom plaštenih stanica.15. The preparation according to claim 12, characterized in that it is used in the treatment of a hyperproliferative disease, wherein the hyperproliferative disease is mantle cell lymphoma. 16. Pripravak prema patentnom zahtjevu 12 naznačen time što se upotrebljava u liječenju hiperproliferativne bolesti, pri čemu je hiperproliferativna bolest difuzni veliki B-stanični limfom.16. The preparation according to patent claim 12, characterized in that it is used in the treatment of a hyperproliferative disease, wherein the hyperproliferative disease is diffuse large B-cell lymphoma. 17. Pripravak prema patentnom zahtjevu 12 naznačen time što se upotrebljava u liječenju hiperproliferativne bolesti, pri čemu je hiperproliferativna bolest folikularni limfom.17. The preparation according to patent claim 12, characterized in that it is used in the treatment of a hyperproliferative disease, wherein the hyperproliferative disease is follicular lymphoma.
HRP20200934TT 2015-07-02 2016-07-01 Solid forms and formulations of (s)-4-(8-amino-3-(1 -(but-2-ynoyl)pyrrolidin-2-yl)imidazo[1,5-a]pyrazin-1-yl)-n-(pyridin-2-yl)benzamide HRP20200934T1 (en)

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Families Citing this family (31)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
RS62713B1 (en) * 2014-08-11 2022-01-31 Acerta Pharma Bv Therapeutic combinations of a btk inhibitor and a bcl-2 inhibitor
JP6829215B2 (en) 2015-07-02 2021-02-10 アセルタ ファーマ ビー．ブイ． (S) -4- (8-amino-3- (1- (gnat-2-inoyl) pyrrolidine-2-yl) imidazole [1,5-a] pyrazine-1-yl) -N- (pyridine-2) -Il) Solid form and formulation of benzamide
HRP20240136T1 (en) 2016-06-29 2024-04-12 Tesaro, Inc. Methods of treating ovarian cancer
WO2018064797A1 (en) * 2016-10-05 2018-04-12 杭州领业医药科技有限公司 Crystal form of acp-196, preparation method therefor and pharmaceutical composition thereof
WO2018115965A1 (en) * 2016-12-23 2018-06-28 Acerta Pharma Bv Solid forms of imidazopyrazine compounds
WO2018148961A1 (en) * 2017-02-20 2018-08-23 杭州领业医药科技有限公司 Crystal form of acp-196 salt and preparation method, pharmaceutical composition, and use thereof
KR20190130625A (en) * 2017-03-27 2019-11-22 테사로, 인코포레이티드 Niraprip formulation
KR20200014736A (en) 2017-03-27 2020-02-11 테사로, 인코포레이티드 Nirapap composition
US10717740B2 (en) 2017-06-13 2020-07-21 Dr. Reddy's Laboratories Limited. Solid forms of acalabrutinib and process for preparation thereof
CA3073293A1 (en) 2017-08-29 2019-03-07 Apotex Inc. Novel crystalline forms of acalabrutinib
CN111278433A (en) 2017-09-26 2020-06-12 特沙诺有限公司 Nilaparib formulations
WO2019105359A1 (en) * 2017-11-30 2019-06-06 苏州科睿思制药有限公司 Crystal form of acalabrutinib, preparation method therefor and application thereof
WO2019134455A1 (en) 2018-01-05 2019-07-11 苏州科睿思制药有限公司 Novel crystal form of acalabrutinib and preparation method and use thereof
WO2019159097A1 (en) * 2018-02-14 2019-08-22 Sun Pharmaceutical Industries Limited Crystalline polymorphic forms of acalabrutinib
CN110650960B (en) * 2018-04-26 2021-08-24 苏州科睿思制药有限公司 Novel crystal form of acalabrutinib and its preparation method and use
EP3587421A1 (en) 2018-06-29 2020-01-01 Sandoz AG Crystalline forms of (s)-4-(8-amino-3-(1-(but-2-ynoyl)pyrrolidin-2-yl)imidazo[1,5-alpha]pyrazin-1-yl-n-(pyridin-2-yl)benzamide
IL281025B2 (en) 2018-08-29 2024-12-01 Acerta Pharma Bv Processes for the preparation of 4-{8-amino-3-[(2S)-1-(but-2-enol)-pyrrolidin-2-yl]imidazo[1,5-a]-pyrazin-1-yl}N-(pyridine-2-yl)-benzamide
WO2020053795A2 (en) 2018-09-13 2020-03-19 Fresenius Kabi Oncology Ltd. Process for the preparation of acalabrutinib and its intermediates
WO2020065667A1 (en) 2018-09-25 2020-04-02 Cipla Limited Novel polymorphs of acalabrutinib, a bruton's tyrosine kinase inhibitor
WO2020198429A1 (en) 2019-03-27 2020-10-01 Assia Chemical Industries Ltd Solid state forms of acalabrutinib
WO2020225831A1 (en) * 2019-05-09 2020-11-12 Msn Laboratories Private Limited, R&D Center Improved process for the preparation of 4-{8-amino-3-[(2s)-1-(but-2-ynoyl)pyrrolidin-2-yl] imidazo[1,5-a]pyrazin-1-yl)}-n-(pyridine-2-yl)benzamide
US12534467B2 (en) 2019-12-02 2026-01-27 Natco Pharma Limited Process for the preparation of Acalabrutinib
WO2021135346A1 (en) * 2019-12-31 2021-07-08 苏州科睿思制药有限公司 New crystal form of acalabrutinib, preparation method therefor and use thereof
WO2021239893A1 (en) 2020-05-29 2021-12-02 Bend Research, Inc. Amorphous solid dispersion of acalabrutinib
PE20230992A1 (en) * 2020-06-19 2023-06-23 Acerta Pharma Bv ACALABRUTINIB MALEATE DOSAGE FORMS
CN112028896A (en) * 2020-10-14 2020-12-04 奥锐特药业(天津)有限公司 Novel crystal form of acatinib and preparation method thereof
WO2022153330A1 (en) * 2021-01-13 2022-07-21 Natco Pharma Limited Pharmaceutical compositions comprising acalabrutinib
WO2023014817A1 (en) 2021-08-03 2023-02-09 Syros Pharmaceuticals, Inc. Compositions and methods for treating lymphomas with a cdk7 inhibitor in combination with a btk inhibitor
WO2023205279A1 (en) * 2022-04-19 2023-10-26 The Johns Hopkins University Improved raman spectroscopy with the addition of aromatic compounds
WO2024164066A1 (en) * 2023-02-09 2024-08-15 Apotex Inc Crystalline forms of acalabrutinib maleate
WO2025125383A1 (en) 2023-12-11 2025-06-19 Synthon B.V. Crystalline forms of acalabrutinib hydrogen maleate

Family Cites Families (48)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2001081031A (en) 1999-08-30 2001-03-27 Schering Ag Benzamide derivative-containing preparation having improved solubility and oral adsorption
US6921763B2 (en) 1999-09-17 2005-07-26 Abbott Laboratories Pyrazolopyrimidines as therapeutic agents
JP2003509427A (en) 1999-09-17 2003-03-11 アボツト・ゲー・エム・ベー・ハー・ウント・コンパニー・カーゲー Kinase inhibitors as therapeutic agents
US6998391B2 (en) 2002-02-07 2006-02-14 Supergen.Inc. Method for treating diseases associated with abnormal kinase activity
RU2405784C2 (en) 2003-10-15 2010-12-10 Оси Фармасьютикалз, Инк. Imidazopyrazines as tyrosine kinase inhibitors
CN1960993A (en) 2004-04-02 2007-05-09 Osi制药公司 6,6-bicyclic substituted heterobicyclic protein kinase inhibitors
ITMI20051231A1 (en) 2005-06-29 2006-12-30 Pharmaproducts Uk Ltd PHARMACEUTICAL FORMULATIONS CONTAINING COLOSTRUM AND FOLINATED CALCIUM FOR THE TREATMENT OF ORAL CABLE AFFECTIONS
KR101655455B1 (en) 2005-09-09 2016-09-07 안젤리니 라보팜 엘엘씨 Trazodone composition for once a day administration
NZ569050A (en) 2005-11-17 2010-11-26 Osi Pharm Inc Fused bicyclic mTOR inhibitors
AR057960A1 (en) 2005-12-02 2007-12-26 Osi Pharm Inc BICYCLE PROTEIN QUINASE INHIBITORS
PE20070855A1 (en) 2005-12-02 2007-10-14 Bayer Pharmaceuticals Corp DERIVATIVES OF 4-AMINO-PYRROLOTRIAZINE SUBSTITUTE AS KINASE INHIBITORS
US7651687B2 (en) 2006-03-13 2010-01-26 Osi Pharmaceuticals, Inc. Combined treatment with an EGFR kinase inhibitor and an agent that sensitizes tumor cells to the effects of EGFR kinase inhibitors
EP2526934B1 (en) 2006-09-22 2015-12-09 Pharmacyclics LLC Inhibitors of bruton's tyrosine kinase
US20120101113A1 (en) 2007-03-28 2012-04-26 Pharmacyclics, Inc. Inhibitors of bruton's tyrosine kinase
EP2954900A1 (en) 2007-03-28 2015-12-16 Pharmacyclics, Inc. Inhibitors of bruton's tyrosine kinase
US8088824B2 (en) * 2007-08-15 2012-01-03 Reata Pharmaceuticals Inc. Forms of CDDO methyl ester
RU2010128239A (en) 2007-12-13 2012-01-20 Новартис АГ (CH) COMBINATIONS OF THERAPEUTIC MEDICINES FOR THE TREATMENT OF CANCER
US9095592B2 (en) 2008-11-07 2015-08-04 The Research Foundation For The State University Of New York Bruton's tyrosine kinase as anti-cancer drug target
US8299077B2 (en) 2009-03-02 2012-10-30 Roche Palo Alto Llc Inhibitors of Bruton's tyrosine kinase
EP2424368B1 (en) 2009-04-29 2014-12-31 Locus Pharmaceuticals, Inc. Pyrrolotriazine compounds
MX2012009208A (en) 2010-02-08 2012-09-07 Msd Oss Bv 8-methyl-1-phenyl-imidazol[1,5-a]pyrazine compounds.
CN102190594A (en) * 2010-03-17 2011-09-21 上海医药工业研究院 Agomelatine hydrogen chloride hydrate and preparation method thereof
UY33288A (en) 2010-03-25 2011-10-31 Glaxosmithkline Llc INDOLINE DERIVATIVES INHIBITORS OF THE PROTEIN QUINASA R OF THE ENDOPLASMATIC RETICLE
TWI500617B (en) 2010-05-31 2015-09-21 Ono Pharmaceutical Co Purine ketone derivatives
CA3240281A1 (en) 2010-06-03 2011-12-08 Pharmacyclics Llc Use of inhibitors of bruton's tyrosine kinase (btk) in the treatment of follicular lymphoma
US20120053189A1 (en) 2010-06-28 2012-03-01 Pharmacyclics, Inc. Btk inhibitors for the treatment of immune mediated conditions
JP6068451B2 (en) 2011-05-17 2017-01-25 ザ・リージエンツ・オブ・ザ・ユニバーシテイ・オブ・カリフオルニア Kinase inhibitor
AU2012275275A1 (en) 2011-06-28 2014-01-23 Pharmacyclics Llc Methods and compositions for inhibition of bone resorption
JP2014520863A (en) 2011-07-13 2014-08-25 ファーマサイクリックス，インク． Inhibitor of Bruton type tyrosine kinase
CA2841887A1 (en) 2011-07-19 2013-01-24 Merck Sharp & Dohme B.V. 4-imidazopyridazin-1-yl-benzamides and 4-imidazotriazin-1-yl-benzamides as btk - inhibitors
ES2950569T3 (en) * 2011-07-19 2023-10-11 Merck Sharp & Dohme (S)-4-(8-amino-3-(1-(but-2-inoyl)pyrrolidin-2-yl)imidazo[1,5-a]pyrazin-1-yl)-2-methoxy-n- (pyridin-2-yl)benzamide as a Btk inhibitor
EP2548877A1 (en) 2011-07-19 2013-01-23 MSD Oss B.V. 4-(5-Membered fused pyridinyl)benzamides as BTK-inhibitors
EP2771010A4 (en) 2011-10-19 2015-04-01 Pharmacyclics Inc USE OF INHIBITORS OF BRUTON TYROSINE KINASE (BTK)
US20140212425A1 (en) 2011-12-05 2014-07-31 Immunomedics, Inc. Therapeutic use of anti-cd22 antibodies for inducing trogocytosis
US8377946B1 (en) 2011-12-30 2013-02-19 Pharmacyclics, Inc. Pyrazolo[3,4-d]pyrimidine and pyrrolo[2,3-d]pyrimidine compounds as kinase inhibitors
WO2013174876A1 (en) * 2012-05-23 2013-11-28 Nerviano Medical Sciences S.R.L. Process for the preparation of n-[5-(3,5-difluoro-benzyl)-1h-indazol-3-yl]-4-(4-methyl-piperazin-1-yl)-2-(tetrahydro-pyran-4-ylamino)-benzamide
WO2014114185A1 (en) 2013-01-23 2014-07-31 Merck Sharp & Dohme Corp. Btk inhibitors
CN105073115A (en) 2013-03-14 2015-11-18 药品循环有限责任公司 Combinations of Bruton's tyrosine kinase inhibitors and CYP3A4 inhibitors
WO2014143807A2 (en) 2013-03-15 2014-09-18 Stromatt Scott Anti-cd37 antibody and bcr pathway antagonist combination therapy for treatment of b-cell malignancies and disorders
HK1215374A1 (en) 2013-04-08 2016-08-26 Pharmacyclics Llc Ibrutinib combination therapy
ES2708350T3 (en) 2013-04-08 2019-04-09 Bayer Pharma AG Use of 2,3-dihydroimidazo [1,2-c] quinazolines for the treatment of lymphomas
WO2015018522A1 (en) 2013-08-06 2015-02-12 Oncoethix Sa Bet-bromodomain inhibitor shows synergism with several anti-cancer agents in pre-clinical models of diffuse large b-cell lymphoma (dlbcl)
WO2015057992A1 (en) * 2013-10-16 2015-04-23 Izumi Raquel Btk inhibitors for hematopoietic mobilization
BR112016012794A2 (en) 2013-12-05 2017-08-08 Acerta Pharma Bv THERAPEUTIC COMBINATION OF A PI3K INHIBITOR AND A BTK INHIBITOR
WO2015086642A1 (en) 2013-12-13 2015-06-18 F. Hoffmann-La Roche Ag Inhibitors of bruton's tyrosine kinase
WO2015110923A2 (en) 2014-01-21 2015-07-30 Acerta Pharma B.V. Methods of treating chronic lymphocytic leukemia and small lymphocytic leukemia usng a btk inhibitor
FR3021783B1 (en) 2014-06-02 2016-05-13 Morpho METHOD FOR VALIDATING THE AUTHENTICITY OF A HUMAN BODY ELEMENT
JP6829215B2 (en) * 2015-07-02 2021-02-10 アセルタ ファーマ ビー．ブイ． (S) -4- (8-amino-3- (1- (gnat-2-inoyl) pyrrolidine-2-yl) imidazole [1,5-a] pyrazine-1-yl) -N- (pyridine-2) -Il) Solid form and formulation of benzamide

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